4^th Global Summit on Toxicology August 24-26, 2015 Philadelphia, USA

Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in\r\nneurotoxicology and neurodevelopmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of\r\nEnvironmental Health. From 2010 to 2012, he was Associated Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute\r\nof Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2012, he got a position as Assistant Professor of Toxicology at\r\nthe Complutense University of Madrid.

4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. There is a great controversy\r\naround the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported.\r\nMoreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal\r\npathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death\r\ninduced by 4-aminipyridine. To provide new sub chronic toxicity data and specifically, evaluate if 4-AP (2, 4 and 10 mg/kg) is able\r\nto induce in vivo cell death process and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic\r\nrange of doses, was conducted in rats. The anatomical pathology, the biochemical and hematological parameters were analyzed. The\r\nleucocytes number, the lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzymatic activity were increased at\r\nall dose but the erythrocytes number, the hemoglobin concentration, the alkaline phosphatase (FAL) and alanine aminotransferase\r\n(ALT) enzymatic activity were increased only at highest dose studied. However, glucose levels decreased at all doses. The biochemical\r\nresults are indicative of hepatic damage. The anatomy pathology studies showed cell death only on liver and kidney. The present work\r\nshows for the first time in vivo cell death on liver and kidney.

Narges Elgolli has completed her PhD from the University of Paris, VII Denis Diderot in France. She is currently an Assistant Professor Doctor at the Faculty of Sciences,\r\nTunis University, in the Laboratory of Aggression Physiology and Endocrine Metabolic Studies, in Tunisia.

Nicotine, contained in classic cigarettes is known to to have a wide variety of deleterious effects. Electronic cigarettes, as a\r\nsubstitute to nicotine, are becoming increasingly popular, although there is no evidence regarding their safety. Considering\r\nthe dearth of information about e-cigarette toxicity, our study was designed to compare nicotine alone to e-liquid with or without\r\nnicotine on lung histopathology in Wistar rats. E-liquid associated or not associated to nicotine and nicotine alone (0.5 mg/kg of\r\nbody weight) were administered intra-peritoneally during 28 days. Histological studies were conducted and hematoxilin-eosin-safran\r\ncoloration test was performed While nicotine treated rats exhibited peri-arteriolar fibrosis, lymphocytes infiltration and arteriolar\r\nobstruction, more critical alterations were observed after the e-liquid without nicotine treatment: Peri-arteriolar and peri-bronchiolar\r\nfibrosis, lymphocytes infiltration, arteriolar obstruction and giant cells. Treatment with e-liquid associated to nicotine led to the same\r\nimportant histo-pathological changes but with additional granulomas. So, e-liquid, per se is able to induce lung toxicity. Furthermore,\r\ne-liquid promotes more damages than nicotine and the combination of the two leads to damages of even more seriousness. E-liquid\r\nmust be used with caution.

Zogopoulos Panagiotis is a Resident of Neurosurgery at the General Hospital of Nikaia-Piraeus “Agios Panteleimon”, Athens, Greece. His ongoing research is in the field\r\nof drugs and their interaction with human brain and cerebral vessels. Several of his papers have been published in reputed peer-review journals and he has presented\r\nvarious researches in international conferences.

Drug abuse represents a significant health issue with tremendous socio-economic consequences. Numerous narcotic substances\r\nexist but most commonly abused ones are heroin, cocaine, cannabis and amphetamine. A broad spectrum of changes affecting\r\nthe central nervous system is observed in drug addicts and it is believed that histopathological changes of the cerebral vessels can lead\r\nto neuronal function deterioration, cognitive decline and psychosocial changes that are seen in drug addicts. We have conducted a\r\npost-mortem (autopsy) study on cerebral vessels of drug abusers comparing them with healthy controls. Histopathological changes\r\nobserved on drug abusers’ cerebral vessels include vascular lumen thrombosis, atherosclerosis, platelet aggregation, transmural\r\nand perivascular infiltration of small cerebral vessels by inflammatory cells, granulomas, dilatation of perivascular spaces with\r\nprotein exudate and fibrinoid necrosis of the medium and intima. These changes are the consequences of vessel wall ischaemia and\r\ncerebrovascular diseases (infection, vasculitis), usually observed on drug abusers and can lead to vascular thrombosis or rupture.\r\nThis study was conducted with the support of IKY Fellowships of Excellence for postgraduate studies in Greece-Siemens Program.

Yosra Dallagi is currently pursuing her PhD at the Faculty of Sciences, Tunis University, in the Laboratory of Aggression Physiology and Endocrine Metabolic Studies, in\r\nTunisia.

Electronic cigarettes, or e-cigarettes, are electrical devices intended to substitute conventional cigarettes, as they simulate the act of\r\nsmoking. These revolutionary systems are currently moot, not only among health professionals but also in the general population,\r\nbecause the lack of data regarding their safety. In this context, our study was performed in order to assess the impact of electronic\r\ncigarette refill liquid (e-liquid) associated or not associated to nicotine at a dose of 0.5 mg/kg of body weight/day or its equivalent of\r\npure nicotine on the central nervous system, particularly on the hippocampus, a critical brain region implied in memory and learning.\r\nTreatments were performed intraperitoneally for 28 days. Two experimental paradigms evaluating memory in rats were used: the\r\nnovel object recognition test and the spontaneous alternation T-maze test. Sub-chronic exposure to e-liquid without nicotine induced\r\ncognitive dysfunctions. In fact, e-liquid, per se, showed an amnesic effect. However, supplementation of nicotine partly restored\r\nthis cognitive decline and partly protected hippocampal neurons against cell death induced by the base e-liquid, highlighting the\r\nneuro-protective effect of nicotine. Cell damages observed after treatment with e-liquid associated to nicotine remain significant,\r\nhighlighting the harmful effects of e-liquid alone. This neurotoxicity, shown by the increase of the activity of lactate deshydrogenase,\r\naccompanied by an increased cerebral calcium level can be at the origin of a cerebral excitotoxicity, leading to hippocampal cells death.\r\nElectronic cigarette has an important neurotoxic potential that could lead to long-term neurodegenerative diseases installation. Its\r\nuse as an anti-smoking alternative must be banned.

Zala Lestan has graduated from the Medical Faculty of the University of Ljubljana in 2014. She has obtained her Medical License in 2015. She is currently involved in\r\nresearch at the Department of Pulmonary Disease and Allergy of the University Medical Center Ljubljana.

The Meza valley, Slovenia has long been contaminated by lead smelting, resulting in widespread lead poisoning in childhood. Due\r\nto behavioral and physiologic charactaristics, young children are most at risk of exposure and long-term negative effects of lead\r\npoisoning. Blood lead levels below the action threshold of 10 μg/dl (Slovenian legislation) or even 5 μg/dl (CDC recommended) are\r\nproven to be in correlation with a reduction of IQ, behavioral and academic problems, hormonal imbalances, growth retardation,\r\narterial hypertension and cumulative cardiovascular risk as well as nephrotoxicity in vulnurable individuals. As these consequences\r\nof lead exposure are usually permanent and long-term detrimental effects are present even after an isolated exposure event due to\r\nthe accumulation of lead in the body, the only feasible way of preventing lead-associated morbidity is to reduce environmental lead\r\nvalues. The potential of mitigating the risk of lead poisoning by remediation of soil with EDTA has been investigated by applying the\r\nIntegrated Exposure Uptake Bio-Kinetic (IUBK) model. The IUBK model predicted that soil remediation would successfully decrease\r\nthe number of locations at which the predicted blood lead level exceeds the stipulated of 10 μg/dl by 90, 38 and 91% respectively, in\r\nthe towns of Mezica, Crna and Zerjav. The mean blood lead level in 3-year old children was predicted to decrease by approximately\r\na half. This reduction is particularly important in the case of Zerjav, where in some areas the values of BLL reach levels over 30 μg/dl\r\nthat can be associated with clinically overt lead poisoning.